■ Chronic systemic infection caused by the spirochete T. pallidum, transmitted through skin and mucosa, with manifestations in nearly every organ system. ■ Incidence is approximately 30,000 cases annually ■ Primary infection: A painless ulcer or chancre on the mucocutaneous site of inoculation. Associated with regional lymphadenopathy (chancriform syndrome: distal ulcer associated with proximal lymphadenopathy). ■ Systemic infection: Shortly after inoculation, syphilis becomes a systemic infection with characteristic secondary and tertiary stages. ■ Course: Clinical course and response to standard therapy may be altered in HIV/AIDS. Venereal syphilis caused by T. pallidum. T. pallidum is a thin delicate spirochete with 6–14 spirals. Only natural host for T. pallidum is the human. Subspecies of T. pallidum cause the nonvenereal diseases endemic syphilis (bejel), yaws, and pinta Transmission. Sexual contact: Contact with infectious lesion (chancre, mucous patch, condyloma latum, cutaneous lesions of secondary syphilis). Sixty percent of contacts of persons with primary and secondary syphilis become infected. Congenital infection: In utero or perinatal transmission. The spirochetes pass through intact mucous membrane and microscopic abrasion in skin, enter lymphatics and blood within a few hours, and produce systemic infection and metastatic foci before development of a primary lesion. Spirochetes divide locally, Spirochetes divide locally, with resulting host inflammatory response and chancre formation, either a single lesion or, less commonly, multiple lesions. Cellular immunity is of major importance in healing of early lesions and control of infection (TH1 type). Dark-Field Microscopy. Positive in primary chancre and papular lesions of secondary syphilis such as condylomata lata. Unreliable in oral cavity because of the presence of saprophytic spirochetes, and negative in patients treated systemically or topically with antibiotics. Regional lymph node aspirated and aspirate examined in the dark-field microscope. Direct Fluorescent Antibody T. pallidum (DFATP) Test Fluorescent antibodies are used to detect T. pallidum in exudate from lesion, lymph node aspirate, or tissue. Serologic Tests for Syphilis (STS). Positive in persons with any treponemal infection. Tests always positive in secondary syphilis. Nontreponemal STS. Measures IgG and IgM directed against cardiolipin– lecithin–cholesterol antigen complex. Rapid plasma reagin (RPR) test (automated RPR: ART). VDRL slide test; nonreactive in 25% of patients with primary syphilis. In early syphilis: either do fluorescent treponemal antibody-absorbed (FTAABS) test or repeat VDRL in 1–2 weeks if initial VDRL negative. Prozone phenomenon: if antibody titer high, test may be negative; must dilute serum; becomes nonreactive or reactive in lower titers following therapy for early syphilis. Treponemal STS FTA-ABS Test. Agglutination assays for antibodies to T. pallidum: Microhemagglutination assay (MHATP; Serodia TPPA test); T. pallidum hemagglutination test (TPHA). Often remain reactive after therapy; not helpful in determining infectious status of patient with past syphilis. Dermatopathology. In primary and secondary syphilis, lesional skin biopsy shows central thinning or ulceration of epidermis. Lymphocytic and plasmacytic dermal infiltrate. Proliferation of capillaries and lymphatics with endarteritis; may have thrombosis and small areas of necrosis. Dieterle stain demonstrates spirochetes. Genital or extragenital lesions occur at sites of inoculation. Ulcers are usually painless unless secondarily infected. Incubation period: 21 days (average); range, 10–90 days. Chancre Button-like papule develops at the site of inoculation into a painless erosion and then ulcerates with raised border and scanty serous exudate . Surface may be crusted. Lesions few millimeters to 1 or 2 cm in diameter. Usually single lesions; less commonly, few, multiple, or kissing lesions. Extragenital chancres occur at any site of inoculatlon; lesions on the fingers may be painful. Sites of Predilection. Genital sites are most common. Male: inner prepuce, coronal sulcus of the glans penis, shaft, base. Female: cervix, vagina, vulva, clitoris, breast; chancres observed less frequently in women. Extragenital chancres: anus or rectum, mouth, lips, tongue tonsils, fingers (painful!), toes, breast, nipple. Lymphadenopathy. Appears within 7 days. Nodes are discrete, firm, rubbery, nontender, and more commonly unilateral; may persist for months. Differential Diagnosis Genital Erosion/Ulcer. GH, traumatic ulcer, fixed drug eruption, chancroid, lymphogranuloma venereum (LGV). Diagnosis Clinical suspicion, confirmed by dark-field microscopy or serologically. Treatment Intramuscular benzathine penicillin G 2.4 million units in single dose or oral doxycycline 100 mg twice daily for 14 days. Appears 2–6 months after primary infection; 2–10 weeks after appearance of the primary chancre; 6–8 weeks after healing of chancre. Chancre may still be present when secondary lesions appear (15% of cases) . Concomitant HIV infection may alter course of secondary syphilis. Fever, sore throat, Concomitant HIV infection may alter course of secondary syphilis. Fever, sore throat, weight loss, malaise, anorexia, headache, meningismus. Mucocutaneous lesions are asymptomatic. Skin Lesions of Secondary Syphilis. Macules and papules 0.5–1 cm, round to oval; pink brownish-red. First exanthem always macular and faint. Later eruptions may be papulosquamous, pustular, or acneiform. Vesiculobullous lesions occur only in neonatal congenital syphilis (palms and soles). On palpation, papules are firm; condylomata lata, soft. Lesions may be annular or polycyclic, especially on face in dark-skinned persons. In relapsing secondary syphilis, arciform lesions. Always sharply defined except for macular exanthem. Lesions are scattered, tend to remain discrete, and usually symmetric Condylomata lata : most commonly in anogenital region and mouth; can be seen on any body surface where moisture can accumulate between intertriginous surfaces, i.e., axillae or toe webs. Hair. Diffuse hair loss, including temples and parietal scalp. Patchy, moth-eaten alopecia on the scalp and beard area. Loss of eyelashes, lateral third of eyebrows Generalized lymphadenopathy. Cervical, suboccipital, inguinal, epitrochlear, axillary. Splenomegaly. Mucous membranes. small, asymptomatic, round or oval, slightly elevated, flat-topped macules and papules 0.5–1 cm in diameter, covered by hyperkeratotic white to gray membrane, occurring on the oral or genital mucosa. Split papules at the angles of the mouth. Associated findings. Musculoskeletal involvement: periostitis of long bones, particularly tibia (nocturnal pain); arthralgia; hydrarthrosis of knees or ankles without x-ray changes. Eyes: acute bacterial iritis, optic neuritis, uveitis. Meningovascular reaction: CSF positive for inflammatory markers. Gastrointestinal (GI) involvement: diffuse pharyngitis, hypertrophic gastritis, hepatitis, patchy proctitis, ulcerative colitis, rectosigmoid mass). Genitourinary involvement: glomerulonephritis and nephrotic syndrome, cystitis, prostatitis. Dermatopathology. Epidermal hyperkeratosis; capillary proliferation with endothelial swelling; perivascular infiltration by monocytes, plasma cells, lymphocytes. Spirochete is present in many tissues including skin, eye, CSE. Liver function. Elevated enzymes. Renal function. Immune complexinduced membranous glomerulonephritis. CSF. Abnormal in 40% of patients. Spirochetes in CSF in 30% of cases. Recurrent eruptions appear after month-long asymptomatic intervals. Initially a relatively faint exanthem, always macular, pink; lesions are ill defined. Later lesions of early syphilis are papular, brownish, and tend to be more localized. Symptoms may last 2–6 weeks (4 weeks average) and may recur in untreated or inadequately treated patients. Secondary lesions subside within 2–6 weeks, infection entering latent stage. Differential Diagnosis Exanthem. Adverse cutaneous drug erupti Exanthem. Adverse cutaneous drug eruption, pityriasis rosea, viral exanthem, infectious mononucleosis, tinea corporis, tinea versicolor, scabies, “id” reaction, condylomata acuminata, acute guttate psoriasis, lichen planus. Clinical suspicion confirmed by lab tests. Darkfield is positive in all secondary syphilis lesions except for macular exanthem. Doxycycline 100 mg twice daily orally for 14 days or ceftriaxone 1g IM once daily for 1014days,or,in special circumstances,azithromycin 2gonce orally. Desensitization, if desensitization is not possible, then erythromycin\ceftriaxone\azithr omycin 1. FITZPATRICK’S Color Atlas and SYNOPSIS OF CLINICAL DERMATOLOGY 7 EDITION. 2. Illustrated Synopsis of Dermatology and Sexually Transmitted Diseases - Neena Khanna. 3. Saurabh Jindal “Review of dermatology ” 2 edition, 2018.